System for compounding and packaging ready to reconstitute ophthalmic drug powders to a solution or to a suspension for administration to an eye of a patient

ABSTRACT

A system and method for mixing compounds is disclosed. Accordingly to one embodiment a transfer device is provided that allows for diluent from a syringe to be introduced into a container having a first compound (e.g., powder) in a sterile manner. In second and third embodiments, systems are shown for combining and mixing first and second compounds contained in first and second containers in a sterile manner. Various dropper tips for dispensing the mixed compounds are disclosed.

CROSS REFERENCE TO RELATED APPLICATION

This application is a continuation application of U.S. application Ser.No. 15/604,429 filed May 24, 2017, which is a divisional application ofU.S. application Ser. No. 14/357,728, filed May 12, 2014, which is anational stage application under 35 U.S.C. § 371, of PCT Application No.PCT/US2013/055153, filed on Aug. 15, 2013, which claims the benefit ofpriority under 35 U.S.C. Section 119(c) of U.S. Application Ser. No.61/684,467, filed on Aug. 17, 2012, U.S. Application Ser. No.61/738,535, filed Dec. 18, 2012, and U.S. Application Ser. No.61/792,792, filed Mar. 15, 2013 and the entire disclosures of each ofthe above identified applications are incorporated herein by referencein their entireties.

BACKGROUND

There is an unmet need for the development of a closed environment forpharmaceutical formulation that will allow healthcare professionals toeasily compound and dispense therapeutically valuable and medicallynecessary medications, that are commercially unavailable due torelatively short drug stability, stringent compounding/manufacturingrequirements and/or lack of proper facilities for sterile preparation ofpharmaceutical products, from powder to a solution/suspension form.

One ophthalmic mixing system that currently exists includes an openenvironment transfer of liquid diluents to an open environment glassbottle with powder that is mixed and then closed with a glass ophthalmicbottle dropper tip with rubber or silicone bulb. This product isavailable as Phospholine Iodide® (echothiophate) from Wyeth-Ayerst. Itis referred to as an open system because it does not contain anyfeatures to prevent the contamination of the product during mixing anduse or to protect the compounder from exposure to the product.

SUMMARY

A new and unique system for compounding, labeling, and dispensing “Readyto Reconstitute Drug Powders or Solutions to Solution or to a Suspensionor to an injectable”. In specific embodiment, the system can be used asan ophthalmic drop delivery container.

In one embodiment, described herein is a Compounding System which makesthe availability of once unstable or non-mixable medications with shortstability dating available to patients worldwide (especially where nospecialty sterile compounding or manufacturing facilities are availablefor the preparation of such medications) for multiple medicalindications. In one embodiment, the system is an Ophthalmic Medication.In one embodiment, the system is for treatment of multiple ophthalmicindications.

The system allows a health care professional or patient to reconstitutepowder or solution with a system that locks together when transferringdiluents solutions to powders or solution a closed environment.

A unique locking and vented diluent transferring device that screws ontoa drug containing bottle with powder minimizes the risk of medicationcontamination or the inhalation of aerosolized powders upon diluenttransfer present in other mixing systems. In one embodiment, the bottleis a bottle for dispensing an ophthalmic drug.

A unique conical design of the diluent solution neck/transfer chamberpermits the solution to be transferred centrally which minimizes run offand spillage when opening.

The sterile easy to screw on dropper tip and outer cap (which allinterlock with the assistance of a locking/dimple/nipple) can be easilyconnected to the reconstitution bottle after opening the sterile packetthat houses both items.

Clear side or bottom panel permits viewing of solution to ensure itmixed properly (no visible signs of incompatibility such as clumping orprecipitation) and permits patient to observe remaining volume as it isused.

In one embodiment, the bottle is adapted with a dropper. In oneembodiment, the drug is contained in Ophthalmic bottles. Ophthalmicbottles are available in clear, opaque, or amber colored combinations toaddress potential drug/light sensitivity issues.

Sterile gloves can be provided for use by the compounder for addedprotection of both the compounded medication and as personal protectiveequipment for the compounder from topical exposure to the medication.

Sterile 70% Isopropyl Alcohol pads are provided for additionaldisinfection at the point of connection between the syringe and thetransfer device and between the transfer device and the drug bottle. Ina specific embodiment, the bottle is an ophthalmic bottle.

Beyond-use date/Discard after date stickers can be provided forplacement onto the final bottle product that has been prepared for useby the patient. In one embodiment, the bottle is an ophthalmic bottle.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features that are characteristic of the present disclosure areexplained in the DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTSSection. The preferred embodiments are best understood by referencingthe following detailed descriptions in connection with the accompanyingdrawings in which:

FIG. 1 is a front view of a fluid transfer system in various stages ofuse according to an embodiment of the invention;

FIG. 1a is a front view of a fluid transfer system in various stages ofuse according to an embodiment of the invention;

FIG. 2 is a front view of a fluid transfer system in various stages ofuse according to another embodiment of the invention;

FIG. 2a is a front view of a fluid transfer system in various stages ofuse according to another embodiment of the invention;

FIG. 3 is a front view of a fluid transfer system in various stages ofuse according to a further embodiment of the invention.

FIG. 4 is an illustration of two variations of a dropper tip drainageport.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention relates to a closed environment pharmaceuticalCompounding System that will allow healthcare professionals to easilycompound and dispense therapeutically valuable and medically necessarytherapeutics that are commercially unavailable due to short stabilitydating or unique compounding requirements, from powder or solution to asolution/suspension form. This closed environment will limit theexposure of the drug to microbial or particulate contaminants carried bythe environment as well as protect the compounder/healthcareprofessional from potential topical or inhalation exposure of themedication (using some present compounding methods or devices). In oneembodiment, the pharmaceutical system is for the preparation of anophthalmic Medication.

Referring to FIG. 1, a sterile vented and two-sided luer-lock andthreaded twist locking transfer device 100 is shown. The transfer device100 includes a vent 126, a luer-lock 128, and threads 130 for twistingand locking engagement to a plastic bottle 102, such as an OphthalmicBottle, that contains a medication in a powder form 140 that is to bemixed from powder into solution/suspension form as set forth in moredetail below. The solution/suspension can be delivery through a dropper,injection, intravenously, or other routes of administration.

FIG. 1 also contains a cross sectional view of the individual pieces(Step 2, Cross Section). Referring to FIG. 1, Step 2 Cross Section, thetransfer device 100 is show in partial cross section (104) threaded ontothe plastic ophthalmic bottle that contains powder 102. A diluentsyringe 106 is shown in cross section connected to the transfer device100 which is connected to the ophthalmic bottle 102.

Referring to FIG. 1, Step 3, a bottle cap 108 and dropper tip 110 areshown in an exploded configuration at 112 and in a configuration withthe bottle cap 108 threaded onto the dropper tip 110 threaded onto theophthalmic bottle 102 at 114.

Referring to FIG. 1, a cap 116 is shown that is typically provided bythe manufacturer. If cap 116 is present, it is removed from theophthalmic bottle with powder 102.

A primary sterility barrier/aluminum seal barrier 118 is removed toexpose the opening of the ophthalmic bottle with powder 102. Onceremoved the surface and rim of the bottle of which the seal sat on canbe cleaned with a sterilizing agent, such as a 70% isopropyl alcoholpads swabbed over the surface, for physical removal of particulates andchemical disinfection.

A secondary sterility barrier 120 of an sterile inert material that willkeep the inner mixing chamber 122 of the ophthalmic bottle with powder102 closed until the membrane 120 is broken by a conical drainage tube124 of the transfer device 100 when the transfer device 100 is connectedto the ophthalmic bottle 102 by turning clockwise until locked byengagement of the threads 130 of the transfer device and the threads 132of the bottle 102.

As shown in FIG. 1, Step 2, the Diluent Syringe 106 is connected at theluer-lock connection point 128 by gently twisting clockwise until lockedin.

Once all three stages have been locked in (i.e., the syringe 106, thetransfer device 100, and the bottle 102) with the assistance of theluer-lock connection 128 and the threads of the ophthalmic bottle's neck132, the syringe arm 134 is slowly pressed down until all the diluent136 is released and transferred to the bottom of the ophthalmic bottle102 where it can be seen through the clear panel 138 for mixture viewingby a compounder (user).

While all 3 stages are still connected the user can slowly rotate thethree pieces clockwise to swirl the powder and solution until the powderdissolves completely (other acceptable mixing motions can be used,including counterclockwise motion, so long as care is taken so not as toprematurely disengage the connected pieces).

Once in solution (e.g., the powder and diluent are mixed), the diluentsyringe 106 can be removed from the transfer device 100, which can inturn be removed from the ophthalmic bottle 102 and discard.

The sterile dropper tip 110 and bottle cap 108 can be provided insterile plastic packaging. After the dropper tip 110 and the bottle cap108 are removed from the sterile packaging they can be attached to theophthalmic bottle 102 with the newly compounded solution or suspension(combination of powder 140 and diluent 136). Care should be taken toavoid contact between the top edge 144 of the ophthalmic bottle 102 withanything but the dropper tip 110. The dropper tip 110 can be rotatedclockwise until the dimple/nipple lock is activated and the dropper tip110 is locked in engagement with the bottle 102. This step should beperformed immediately after the bottle 102 has been separated from thesyringe 106 and the transfer device 100 in order to limit exposure ofthe opened container to particulate matter and microbial organisms thatmay compromise the sterility of the solution/suspension.

Cap 108 can be placed onto the dropper tip 110 and rotated such that thethreads 146 of the dropper tip 110 and the internal threads (not shown)of the cap 108 engage until closed. The locked and complete cap 108,dropper tip 110, and ophthalmic bottle 102 combination can be seen at114 in FIG. 1. The bottle 102 can include a label 148 that can be usedto identify the contents of the bottle and contents can be dispensedthrough the top 142 of dropper 110.

FIG. 1A shows as system that is similar to the system shown in FIG. 1.As shown in FIG. 1A, a transfer device 100 a is provided with a drainagetube 128 a that has a more sharply angled shape. A drainage tube havinga shape as shown in FIG. 1A is advantageous for piercing membranes 124 abecause less force will be required to puncture the membrane 124 a dueto the sharper point shape. In addition, the drainage tube 128 a canalso be advantageous for piercing thicker and/or reinforced membranes.

FIG. 2 shows a two-sided diluents transferring spike with threadedtransfer device 200 that can be used between two ophthalmic bottles, 202and 204 in which a first ophthalmic bottle 202 contains a drug powder206 to be mixed and a second bottle 204 containing pre-measured diluent208 that can be used for compounding the powder to solution/suspension.The transfer device 200 includes a spike 210 that has fluid transferports 212 and 214 that allow the diluent solution to flow more easily aswell as a vent 216 for preventing negative pressures that can impede theflowing of the diluents from one bottle to another. The transfer device200 includes at the other end of spike 210 a drainage tube 224.

Referring to FIG. 2, Step 1, once the caps 218 and aluminum seals/foils220 have been removed (shown in place on bottle 202 and removed frombottle 204), the bottles top surfaces and edges of the two bottles canbe disinfected with 70% isopropyl alcohol. The inner sterility membrane222 of the bottle 202 containing the powder is punctured by the drainagetube 224 of the transfer device 200 to allow the transfer of diluentsfrom one bottle to the other so the powder can be mixed into solution.In one example, this is accomplished by first attaching bottle 204containing the diluents solution 208 to the vented transfer device 200and then the bottle 202 containing the powder 206 is carefully twistedonto the vented transfer device 200 using the threaded or beveled edges226 of the bottles that twists onto the threads 228 of the transferdevice 200. After connecting bottles 202 and 204 to the transfer device200, bottles and transfer device are inverted so that the diluent bottle204 is on top with respect to the powder containing bottle 202 as shownin FIG. 2, Step 2 and Step 2 Cross Section. In this configuration, thediluent solution, via gravity, passes through the connector spike 210and the conical drainage tube 224 of the transfer device 200. Bottle 202and 204 can each include a clear viewing panel 230 that can be used toview the diluent, the powder, and the transfer of the diluent into thepowder containing bottle. After the diluent has been transferred to thepowder containing bottle and with the two bottles still connected viathe transfer device, the assembly can be gently swirled clockwise untilthe drug is in solution or uniformly mixed in the case of suspensions.Panel 230 of bottle 202 can be used to confirm proper mixing. Finally,as shown in Step 3, the bottle that contained the diluents 204 and thetransfer device 200 are separated from bottle 202 and discarded. Adropper tip 232 is twisted on until locked and then the dropper cap 234is placed onto the tip and turned clockwise until locked.

FIG. 2A shows as system that is similar to the system shown in FIG. 2.As shown in FIG. 2A, a transfer device 200 a is provided with a drainagetube 224 a that has a more sharply angled shape. A drainage tube havinga shape as shown in FIG. 2A is advantageous for piecing membranes 222 abecause less force will be required to puncture the membrane 222 a dueto the sharper point shape. In addition, the drainage tube 224 a canalso be advantageous for piercing thicker and/or reinforced membranes.In addition, spike 210 a can be provided with additional fluid transferports 214 a. These ports help the diluent to drain from the bottle inless time and the location of fluid transfer ports 214 a helps ensurethat all (or nearly all) of the diluent is drained from the bottle.Moreover, spike 210 a is show with a slightly shorter configuration sothat the tip of the spike 210 a does not extend past the end of transferdevice 200 a. This configuration in which the spike 210 a is more fullyshrouded helps prevent inadvertent contact of the spike 210 a withcontaminants and non-sterile surfaces.

FIG. 3 displays an embodiment of two ophthalmic bottles (one containinga diluent 300 and another containing a powder 302 which will be mixedinto solution or into a suspension). The bottle 300, 302 include caps304, 306 and protective foils 308, 310 that are removed prior to the twobottles being connected together. After the caps and foils are removed,one bottle is twisted onto the opening of the other bottle until bothbottles are locked together, as shown in Step 2. One bottle can includeinternal grooves 314 and the other can include corresponding externalgrooves 316 that facilitate the twisting engagement between the bottles.A conical transfer tube 312 allows the diluents to drain from one bottle300 to the bottle containing the powder 302. The contents of the bottlecan be viewed through the side or bottom viewing panel 318. The bottlescan be swirled clockwise while still connected so that the powder ismixed into solution or suspension. After the mixing, the top bottle 300that formally contained the diluents can be removed and discard. Adropper tip 320 can twist on to the threads 316 of bottle 302 nowcontaining the powder/diluent mixture by twisting clockwise until lockedinto place. The dropper tip 320 may or may not contain an additionalfilter if needed for filtering solution as it is squeezed out by thepatient when self-administering the drops (if needed). A traditionalsnap in tip may also be used however the screw on is preferred for addedsecurity. A sterile dropper cap 322 can be screwed onto the dropper tip320 for easy closing and opening.

FIG. 4 displays an embodiment of different ophthalmic dropper tips 400and 402 that may be used in the event that the broken internal sterilitymembrane/barrier (e.g., barrier 120, 222 in FIGS. 1 and 2, respectively)(inside the ophthalmic bottle that contains the powdered solution)decreases or blocks the flow of the solution upon use. The dropper tip400 includes a spike end 404 that include an open end in fluidcommunication with draining ports 406. Dropper tip 402 is similar exceptit includes a relatively flat bottom end 408. Dropper tip 402 includesdraining ports 410. Both dropper tips 400 and 402 are configured to beremovable engageable with a protective cap 412.

Beyond-use date/discard after date stickers which are provided forplacement onto the final ophthalmic bottle that has been prepared foruse by the patient have not been displayed in the drawings as they varyin style and color.

This ready-to-mix and dispense medication compounding system provides: apre-measured sterile diluent in a syringe that luer locks onto a sterilevented transfer device (transfer device contains a vented pin thatfilters air and other particles while preventing a negative pressureenvironment that would affect the flow of the diluent solution into thebottle) that twists on with threads and connects onto a plastic bottlewith medication in a powder form for mixing. In one embodiment, themedication is an ophthalmic medication.

In another embodiment the vented transfer device may include a separateinjection port to permit injecting an additional substance (solution ormedication) into the mixing chamber without disconnecting the primarysyringe with solution that has been luer locked into the bottle thatcontains the powder or solution. This cap will likewise be screwed ontill locked.

Bottle sizes may vary from 2.5 mL to 30 mL depending on the final volumerequired.

A primary sterility barrier (aluminum seal under the capped ophthalmicbottle containing the powder as supplied by the manufacturer).

A secondary sterility barrier (internal membrane within the neck of thedrug powder bottle) for the protection of the medication while preparingfor mixing. This secondary barrier will be made of an inertnon-reactive, sterile, material that will maintain its integrity untilthe drainage cone, upon connection of the transfer device, pierces thecenter of the membrane thus causing it to snap into two exposing theinner mixing chamber with the powder to the diluents when the syringe ispressed. In an embodiment, the drug is an ophthalmic drug.

A unique conical drainage tube that will minimize spillage and furtherfacilitate the flowing of the diluents towards the powder within themixing chamber of the bottle. In one embodiment, the bottle is adaptedwith a dropper. In one embodiment, the bottle is an ophthalmic bottle.

A see through plastic window (include on the side or bottom of thebottle which allows the compounder to look at the solution so it ismixed properly).

In one embodiment, the system also includes a unique threaded steriledropper tip and cap. In one embodiment, the sterile dropper tip containsa special lock-on dimple/nipple that will protect the dropper tip frombeing opened and spilling of the drug solution or compromising thesterility of the solution once compounded and dispensed. In oneembodiment, the system is for patient drug administration into the eye.A snap-on type tip may also be used however the screw on is preferredfor added security and prevention of tampering. The dropper tip willhave internal and external threads for twisting onto the ophthalmicbottle and for twisting the cap onto the dropper tip. The steriledropper cap will then screw onto the dropper tip for easy closing andopening.

Beyond-use/Discard after labels can also be provided to be used on thebottle so the patient will remember the assigned expiration/discard dateof the drug.

The above described system can be provided in a kit that also containssterile latex or non-latex gloves and 70% isopropyl alcohol pads foradditional disinfecting of connector points and surfaces.

Additional safeguards and good techniques for compounding sterileproducts, such as those listed in the United States Pharmacopeia <797>guidelines, should be followed, where applicable, for added protectionof the medication and the compounder i.e., wearing of a face mask.

Ultimately, a complete labeled, and ready-to-use bottle will bedispensed to the patient, for use and storage, by pharmacies, hospitals,clinics and other healthcare settings. In one embodiment, the bottle isan ophthalmic bottle.

In one embodiment, the disclosed system may be used for such medicationsas piperacillin-tazobactam, vancomycin, metronidazole, macrolideantibiotics, aztreonam, amphotericin B in conventional (desoxycholate)or liposomal forms, imipenem-cilastatin, ceftazidime, cefazolin, andother penicillins, cephalosporins or other related or non-relatedantimicrobial medications. Other medications that may be compoundedusing this system include antineoplastic/chemotherapeutic(5-fluorouracil, mitomycin, etc.) agents and other ophthalmic classes ofmedications. This system may be used together or without injectablemedications such as those mentioned above as continuation of therapypost surgical or non surgical ophthalmic procedures. SEE TABLE 1 for thelist of products that may be used with the system.

TABLE 1 Antibiotics Class Generic/Brand Lipopeptides Daptomycin(Cubicin) Fluoroquinolone Gemifloxacin (Factive) LipoglycopeptidesTelavancin (Vibativ), 2009 Cephalosporin Ceftaroline (Teflaro), 2010(5th generation) Macrocyclics Fidaxomicin (Dificid), 2011 Generic BrandName Aminoglycoside Antibiotics Amikacin Amikin Gentamicin Garamycin,G-Mycin, Jenamicin Kanamycin Kantrex Neomycin Mycifradin, MyciguentNetilmicin Netromycin Paromomycin Streptomycin Tobramycin NebcinCephalosporins First Generation Cefacetrile (cephacetrile) Celospor,Celtol, Cristacef Cefadroxil (cefadroxyl) Duricef, Ultracef Cefalexin(cephalexin) Keflex, Keftab Cefaloglycin (cephaloglycin) KefglycinCefalonium (cephalonium) Cefaloridine (cephaloradine) Cefalotin(cephalothin) Keflin Cefapirin (cephapirin) Cefadyl CefatrizineCefazaflur Cefazedone Cefazolin (cephazolin) Ancef, Kefzol Cefradine(cephradine) Velosef Cefroxadine Ceftezole Second Generation CefaclorCeclor, Ceclor CD, Distaclor, Keflor, Ranicor Cefamandole MandolCefmetazole Cefonicid Monocid Cefotetan Cefotan Cefoxitin MefoxinCefprozil (cefproxil) Cefzil Cefuroxime Ceftin, Kefurox, Zinacef, ZinnatCefuzonam Third Generation Cefcapene Cefdaloxime Cefdinir Omnicef,Cefdiel Cefditoren Spectracef Cefetamet Cefixime Suprax CefmenoximeCefmax Cefodizime Cefotaxime Claforan Cefpimizole Cefpodoxime VantinCefteram Ceftibuten Cedax Ceftiofur Excede Ceftiolene CeftizoximeCefizox Ceftriaxone Rocephin Cefoperazone Cefobid Ceftazidime Ceptaz,Fortum, Fortaz, Tazicef, Tazidime Fourth Generation Cefclidine CefepimeMaxipime Cefluprenam Cefoselis Cefozopran Cefpirome Cefrom CefquinomeNot Classified Cefaclomezine Cefaloram Cefaparole Cefcanel CefedrolorCefempidone Cefetrizole Cefivitril Cefmatilen Cefmepidium CefovecinCefoxazole Cefrotil Cefsumide Cefuracetime Ceftioxide CarbapenemsImipenem, Imipenem/cilastatin Primaxin Doripenem Doribax MeropenemMerrem Ertapenem Invanz Quinolone Antibiotics First GenerationFlumequine Flubactin Nalidixic acid NegGam, Wintomylon Oxolinic acidUroxin Piromidic acid Panacid Pipemidic acid Dolcol Rosoxacin EradacilSecond Generation Ciprofloxacin Cipro, Cipro XR, Ciprobay, CiproxinEnoxacin Enroxil, Penetrex Lomefloxacin Maxaquin Nadifloxacin Acuatim,Nadoxin, Nadixa Norfloxacin Lexinor, Noroxin, Quinabic, JanacinOfloxacin Floxin, Oxaldin, Tarivid Pefloxacin Peflacine RufloxacinUroflox Third Generation Balofloxacin Baloxin Gatifloxacin Tequin, ZymarGrepafloxacin Raxar Levofloxacin Cravit, Levaquin Moxifloxacin Avelox,Vigamox Pazufloxacin Pasil, Pazucross Sparfloxacin Zagam TemafloxacinOmniflox Tosufloxacin Ozex, Tosacin Fourth Generation BesifloxacinBesivance Clinafloxacin Gemifloxacin Factive Sitafloxacin GracevitTrovafloxacin Trovan Prulifloxacin Quisnon Macrolide AntibioticsAzithromycin Zithromax Erythromycin Clarithromycin Biaxin DirithromycinDynabac Roxithromycin Rulid, Surlid Ketolides Telithromycin KetekPenicillins Amoxicillin Amoxil, Polymox, Trimox, Wymox AmpicillinOmnipen, Polycillin, Polycillin-N, Principen, Totacillin BacampicillinSpectrobid Carbenicillin Geocillin, Geopen Cloxacillin CloxapenDicloxacillin Dynapen, Dycill, Pathocil Flucloxacillin Flopen, Floxapen,Staphcillin Mezlocillin Mezlin Nafcillin Nafcil, Nallpen, UnipenOxacillin Bactocill, Prostaphlin Penicillin G Bicillin L-A, Crysticillin300 A.S., Pentids, Permapen, Pfizerpen, Pfizerpen-AS, WycillinPenicillin V Beepen-VK, Betapen-VK, Ledercillin VK, V-Cillin KPiperacillin Pipracil Pivampicillin Pivmecillinam Ticarcillin TicarSulfonamides Sulfamethizole Thiosulfil Forte Sulfamethoxazole Gantanol,Urobak Sulfisoxazole Gantrisin Trimethoprim- Sulfamethoxazole Bactrim,Bactrim DS, Cotrim, Cotrim DS, Septra, Septra DS, Sulfatrim,Sulfatrim-DS Tetracycline Antibiotics Demeclocycline DeclomycinDoxycycline Doryx, Vibramycin Minocycline Dynacin, Minocin, MonodoxOxytetracycline Terramycin Tetracycline Achromycin GlycylcyclinesTigecycline Tygacil Other Antibiotics Vancomycin Vancocin MetronidazoleFlagyl, Helidac, Metizol, Metric 21, Neo-Metric, Noritate, NovonidazolTinidazole Tindamax Nitrofurantoin Furadantin, Macrobid, MacrodantinChloramphenicol Chloromycetin Oxazolidinones Linezolid Zyvox RifamycinsRifampin Rifadin Rifabutin Mycobutin Rifapentine Priftin LincosamidesClindamycin Cleocin Lincomycin Lincocin Streptogramins PristinamycinPyostacine Quinupristin/dalfopristin Synercid

Fortified ophthalmic drops of cephalosporins, combination groups ofantibiotics listed above, sodium sulfacetamide, acyclovir, cidofivir,ganciclovir, idoxuridine, trifluridine, amphotericin, clotrimazole,fluconazole, flucytosine, ketoconazole, miconazole, natamycin,voriconazole, Thiotepa, 5-fluorouracil mitomycin, paclitaxol,tetrahydonannabino marijuana (THC), cocaine, glycerin,hydroxyamphetamine, rose bengal solution, brilliant blue, indocyaninegreen (ICG) solution, albumin, autologous serum eye drops, cyclosporinewith or without combination medications, methyl cellulose, tacrolimus,antioxidant/vitamin mixtures, acetazolamide, preservative-free eye dropswhich may include: include apraclonidine, betaxolol, bimatoprost,brimonidine, carbachol, clonidine, dipivefrin, dorzolamide, epinephrine,latanoprost, levobutanol, phospholine iodide, pilocarpine, pilocarpinecombinations, travoprost, dexamethasone, methylprednisolone,prednisolonoe, rimexolone, triamcinolone, acetylcysteine, aminocaproicacid, bevacizumab, brilliant green, brilliant blue, dicofenac,ethylenediaminetetraacetic acid (EDTA), glutathione, interferon,polyhexamethylene biguanide (PHMB), physostigmine, povidone-iodine,silver nitrate, sodium chloride, sterile water or artificial tearcombination product with or without methylcelluslose, tetrahydrolazine,vitamins, atropine, benoxinate, cylcopentolate, cyclopentolatecombinations, cyclopentolate/phenylephrine, dapiprazole, homatropine,lidocaine, phenylephrine, proparacaine alone or in combination withother drugs, scopolamine, tetracaine, tropicamide, tropicamidecombinations with cyclopentolate or phenylephrine,

In another embodiment, the vented transfer device, with or withoutadditional injection port may be sold as a part of a commerciallyavailable kit. These bottles can contain the vented transfer device, thebottle for mixing (which will be empty and not be provided with anypowder or solution for mixing), with a twist on cap (which contains thespecial locking device), and the cap for closing the final compoundedproduct. It can be made available as a retail product for retailpharmacy, the pharmaceutical market, or academic, institutional,research or public settings which require bottles for mixing eyeproducts or non-eye products that requires protection of the product andthe individual while mixing a powder to solution or a solution tosolution in any setting. This system can also be considered for use inmixing other artistic, cosmetic, commercial or industrial products suchas creams, gels, solutions, paints and glues.

According to one embodiment and referring to FIG. 1, a system for mixingcompounds includes a first container 102 for containing a first compound140. The first compound can be a drug in powder form. The firstcontainer 102 has a collar 132 that defines an opening into an interiorof the container. A membrane 120 is disposed over the opening of thecontainer 102. The membrane 120 is capable of being punctured in orderto provide fluid communication to an interior of the container. Themembrane 120 can be a metal foil, for example. A sleeve portion of thetransfer device 100 is provided that is sized and shaped to removablyengage the collar of the first container 102. The sleeve can includeinternal threads 130 that engage external threads 132 around the collarof the container as shown. A puncture member 124 is disposed on a firstside of the sleeve. The puncture member sized and shaped to puncture themembrane in a first condition in which the sleeve is engaged with thecollar (e.g., as the sleeve is threaded onto the collar, the puncturemember is lowered relative to the membrane and advanced until themembrane is punctured. A luer lock fitting 128 is disposed on a secondside of the transfer device 100 opposite the first side. The luer lockis sized and shaped to allow a syringe 106 to engage to the luer lock.The luer lock and the puncture member define a fluid communicationpassage such that fluid can be delivered through the luer lock and thepuncture member and into the container when the sleeve is engaged to thecollar. Accordingly, a syringe containing a second compound (e.g., adiluent fluid) can be engaged with the luer lock and the fluid in thesyringe can be dispensed through the fluid communication passage andinto the first container where it can mix with the first compoundcontained within the container.

A vent member 126 can be included that provides a fluid communicationpassage through a wall of the sleeve such that when the sleeve is in afirst condition and engaged with the collar of the container air can beexpelled from the container through the vent as fluid is introduced intothe container through the luer lock. The vent can include a one-wayvalve that permits air in the container to be expelled and does notpermit air to enter the container from the outside environment.

A protective cap 116 can also be included that is sized and shaped to beremovably disposed over the membrane. The protective cap providesadditional protect against inadvertent puncture of the membrane andbeing removable prior to engagement of the sleeve with the collar. Theprotective cap can be a removable plastic disk, for example.

After the sleeve is removed from the collar, a dropper tip 110 that issized and shaped to be removably engaged to the collar such that thedropper tip can be attached to the first container. The dropper tippermits controlled dispensing of a mixture of the first compound and afluid introduced into the first container through the luer lock.Referring to FIG. 4, the dropper tip can include a drain port that isdisposed on an underside thereof. The drain port is sized and shaped topass through the membrane when the dropper tip is engaged with thecollar. The drain port provides a fluid communication passage throughthe drain port to a dispensing end of the dropper tip.

The system of FIG. 2 is similar to FIG. 1 but permits connection of asecond container to the sleeve. The sleeve/transfer device 200 is atwo-sided sleeve in that it includes threads for engagement of first andsecond containers 202, 204. The puncture member 210, 224 is also twosided in that it extends in both directions so that it can puncture themembranes of the first and second containers when the containers areengaged to the sleeve. The puncture member also defines two fluidpassages, one to allow fluid transfer and one to provide equalization ofpressure between the two containers as fluid is transferred. Forexample, as fluid is emptied from the second container into the first,are from the first container passes into the second. This prevents avacuum from developing that would hinder transfer of fluid. In addition,a vent 216 is also provided to provide pressure equalization.

The system of FIG. 3 includes a sleeve that is integral with the secondcontainer. The sleeve is sized and shaped to removable engage with thecollar of the first container. The collar of the second container issized and shaped (e.g., tapered) such that it can puncture the membraneof the first container and enter into the collar of the first container.

The systems shown in FIGS. 1, 2, and 3 can be used to mix compounds ofceftazidime or vancomycin. For example, the first container can includevancomycin as the first compound and a diluting fluid can be added tothe first container to mix into a medical treatment solution.

Directions for Use in a Specific Embodiment

-   -   1) In a clean and quiet area remove contents of kit and put on        latex or non-latex containing compounding gloves. You may choose        to also put on a surgical facial mask if available.    -   2) Remove bottle with drug powder (i.e. antibiotic) and remove        the plastic cap and then the pressure sensitive aluminum        security seal. Clean top with 70% isopropyl alcohol pad.    -   3) Remove the sterile vented transfer-connector from plastic        wrapper and screw onto neck of ophthalmic bottle with powder        until locked. This will break the inner membrane which maintains        sterility of the inner chamber with powder.    -   4) Assemble the pre-filled syringe with diluent. Uncap syringe        end and remove foil. Swab top with 70% isopropyl alcohol pad and        then screw on/attach to the luer-lock top of the vented        transfer-connector.    -   5) Slowly inject diluent into bottle powder vial and then (while        still connected) swirl the contents of the mixture clockwise        until the solution is clear or uniformly mixed in the case of        suspensions. Do not shake. (view solution from clear side or        bottom window panel). Once in solution/suspension unscrew the        transfer-connector and syringe and discard.    -   6) Remove combined outer cap and Inner dropper tip from sterile        plastic wrapping (without touching connection base to maintain        sterility) and screw tip first and then cap onto the neck of the        bottle until each lock into place. Ensure that both cap and        dropper heads are tightened properly.    -   7) A Beyond-use Label with a discard after date is provided for        the pharmacist or the physician to write the date in which the        mixed solution or suspension will expire on and should be thrown        out (see package insert for recommended expiration date).    -   8) In one embodiment, the bottle is an ophthalmic bottle.

Each kit to be commercially supplied as:

-   -   1) Bottle with drug as powder    -   2) Pre-filled syringe with diluent for mixing    -   3) Sterile vented transfer-connector    -   4) Sterile screw on dropper tip and sterile outer cap    -   5) Pads saturated with 70% isospropyl alcohol.    -   6) Beyond-use label with discard after date to be filled out and        affixed after mixing.    -   7) Sterile latex or non-latex gloves for compounding.    -   8) In one embodiment, the bottle is an ophthalmic bottle.

This ready-to-mix and dispense medication compounding system provides: apre-measured sterile diluent in a syringe that luer locks onto a sterilevented transfer device that twists on and connects onto a bottle withmedication in a powder form for mixing, a primary and secondarysterility barrier found in the bottle, a unique drain spout, and a seethrough plastic window for viewing of the product while mixing. In oneembodiment, this system also includes a unique threaded sterile droppertip and cap. The sterile dropper tip contains a special lock-ondimple/nipple that will protect the dropper tip from opening andspilling of the drug solution or compromising the sterility of thesolution once compounded and dispensed. In one embodiment, a traditionalsnap-on tip may also be used, however, the screw on is preferred foradded security. The sterile dropper cap will then screw onto the droppertip for easy closing and opening. Beyond-use stickers/labels are alsoprovided to be used on the bottle so the patient will remember theexpiration/discard date of the drug. Also provided is a kit comprisingthe disclosed system and contains sterile latex or non-latex gloves and70% isopropyl alcohol pads to minimize the risk of extrinsiccontamination of connector locations. Ultimately a complete, labeled,and ready-to-use bottle will be dispensed to the patient, for use andstorage, by pharmacies, hospitals, clinics and other healthcaresettings. The system may be used for compounding such medications aspiperacillin-tazobactam, vancomycin, metronidazole, macrolideantibiotics, aztreonam, amphotericin B (in desoxycholate or liposomalformulations), imipenem-cilastatin, ceftazidime, cefazolin, and otherpenicillins, cephalosporins or other related or non-relatedantimicrobial medications. Other medications that may be compoundedusing this system include antineoplastic chemotherapeutic agents andother ophthalmic classes of medications. In specific embodiment, thesystem is for ophthalmic medication.

The invention is not to be limited in scope by the specific embodimentsdescribed herein. Indeed, various modifications of the invention inaddition to those described will become apparent to those skilled in theart from the foregoing description and accompanying figures. Suchmodifications are intended to fall within the scope of the appendedclaims.

All references cited herein are incorporated herein by reference intheir entirety and for all purposes to the same extent as if eachindividual publication or patent or patent application was specificallyand individually indicated to be incorporated by reference in itsentirety for all purposes.

What is claimed is:
 1. A method for sterilely mixing compounds toprovide an ophthalmic compound for administration to an eye of apatient, the method comprising the steps of: obtaining a firstcontainer, the first container containing a first compound, the firstcontainer having a collar defining an opening and a membrane disposedover the opening of the container, wherein the membrane is capable ofbeing punctured in order to provide fluid communication to an interiorof the container; engaging a sleeve with the collar of the firstcontainer, the sleeve including a puncture member disposed on a firstside of the sleeve and a luer lock disposed on a second side of thesleeve opposite the first side, the luer lock and the puncture memberdefining a fluid communication passage such that fluid can be deliveredthrough the luer lock and the puncture member and into the container;puncturing the membrane with the puncture member by engagement of thesleeve with the collar; engaging a second container with the luer lock,the second container containing a fluid; introducing the fluid into thefirst container through the luer lock and sleeve; venting air from thefirst container through a vent member that provides a fluidcommunication passage through a wall of the sleeve as the fluid isintroduced into the first container; agitating the first container tocreate a mixture of the first compound and the fluid; disengaging thesecond container and sleeve from the first container; engaging a droppertip with the collar, the dropper tip being sized and shaped to removablyengage the collar and having a complementary structure to the sleevesuch that the dropper tip can be attached to the first container withthe sleeve removed from the first container, the dropper tip having astatic open lumen and a drain port disposed on an underside of thedropper tip, the drain port being sized and shaped to pass through themembrane and provide a fluid communication passage through the drainport to a dispensing end of the dropper tip; and dispensing, in acontrolled manner directly from the first container through the droppertip to the patient eye, the mixture of the first compound and the fluid,wherein the first container is at least partially deformable tofacilitate dispensing.
 2. The method of claim 1, wherein the length ofthe vent is smaller than the diameter of the sleeve.
 3. The method ofclaim 1, wherein a protective cap is disposed over the membrane, theprotective cap providing additional protection against inadvertentpuncture of the membrane, further including the step of removing theprotective cap prior to engaging the sleeve with the collar.
 4. Themethod of claim 1, wherein the second container is a syringe.
 5. Themethod of claim 1, wherein the collar and the sleeve include threadsthat permit the removable engagement of the collar and sleeve.
 6. Themethod of claim 1, wherein the vent includes a one-way valve thatpermits air in at least one of the first and second containers to beexpelled and does not permit air, microbes and a combination thereof toenter at least one of the first and second containers from the outsideenvironment.
 7. The method of claim 1, wherein the fluid is a diluentfor mixing with the first compound.
 8. The method of claim 1, whereinthe dropper tip includes a filter to prevent outflow of at least one ofmicrobes, contaminants, unmixed drug and a combination thereof from thefirst container into a patient eye.
 9. The system of claim 8, whereinthe filter is a 5 micron filter.
 10. The method of claim 1, wherein atleast a portion of the first container is translucent such that contentsof the first container can be viewed through the translucent portion.11. The method of claim 1, wherein at least a first portion of the firstcontainer is opaque and at least a second portion is translucent suchthat contents of the first container can be viewed through thetranslucent portion.
 12. The system of claim 1, wherein the dropper tipincludes a locking mechanism to selectively, lockingly engage with thecollar.
 13. The system of claim 1, wherein the patient is a human ornon-human animal.
 14. A method for sterilely mixing compounds to providean ophthalmic compound for administration to an eye of a patient, themethod comprising the steps of: obtaining a first container, the firstcontainer containing a first compound, the first container having acollar defining an opening and a membrane disposed over the opening ofthe container, wherein the membrane is capable of being punctured inorder to provide fluid communication to an interior of the container;engaging a sleeve with the collar of the first container, the sleeveincluding a puncture member disposed on a first side of the sleeve;puncturing the membrane with the puncture member by engagement of thesleeve with the collar, engaging a second container with the sleeve, thesecond container containing a fluid; introducing the fluid into thefirst container through the sleeve; venting air from the first containerthrough a vent member that provides a fluid communication passagethrough a wall of the sleeve as the fluid is introduced into the firstcontainer; agitating the first container to create a mixture of thefirst compound and the fluid; disengaging the second container andsleeve from the first container; engaging a dropper tip with the collar,the dropper tip being sized and shaped to removably engage the collarand having a complementary structure to the sleeve such that the droppertip can be attached to the first container with the sleeve removed fromthe first container, the dropper tip having a static open lumen and adrain port disposed on an underside of the dropper tip, the drain portbeing sized and shaped to pass through the membrane and provide a fluidcommunication passage through the drain port to a dispensing end of thedropper tip; and dispensing, in a controlled manner directly from thefirst container through the dropper tip to the patient eye, the mixtureof the first compound and the fluid, wherein the first container is atleast partially deformable to facilitate dispensing.
 15. The method ofclaim 14, wherein the length of the vent is smaller than the diameter ofthe sleeve.
 16. The method of claim 14, wherein a protective cap isdisposed over the membrane, the protective cap providing additionalprotection against inadvertent puncture of the membrane, furtherincluding the step of removing the protective cap prior to engaging thesleeve with the collar.
 17. The method of claim 14, wherein the secondcontainer is an ophthalmic bottle.
 18. The method of claim 14, whereinthe second container includes a collar defining an opening and amembrane disposed over the opening of the second container, and thesleeve includes a second puncture member, wherein the membrane of thesecond container is punctured by the second puncture member as a resultof the engagement of the second container with the sleeve.
 19. Themethod of claim 14, wherein the vent includes a one-way valve thatpermits air in at least one of the first and second containers to beexpelled and does not permit air, microbes and a combination thereof toenter at least one of the first and second containers from the outsideenvironment.
 20. The system of claim 14, wherein the patient is a humanor non-human animal.
 21. The system of claim 14, wherein the dropper tipincludes a locking mechanism to selectively, lockingly engage with thecollar.